The signaling cascades of Ganoderma lucidum extracts in stimulating non-amyloidogenic protein secretion in human neuroblastoma SH-SY5Y cell lines.
Ganoderma lucidum (GL) is a medicinal mushroom that possesses various pharmacological properties which are also documented in the ancient reports where GL is praised for its effects on the promotion of health and longevity. In this study, we have investigated the effect of GL mycelia extracts on the non-amyloidogenic protein secretion (sAPPalpha) and the amyloid precursor protein (APP) expression in SH-SY5Y neuroblastoma cells. In order to characterize the signaling pathway which mediates GL-enhanced sAPPalpha secretion, we used inhibitors of nerve growth factor (NGF) signaling pathways, phosphatidylinositol 3 kinase (PI3K), phospholipase Cgamma1 (PLCgamma1), protein kinase C (PKC) and extracellular signal-regulated kinase (ERK1/2), to block GL-mediated sAPPalpha secretion as well as ERK1/2 and PKC activation by using Western blot analysis. Our results provided for the first time evidence that GL mycelia extracts increased APP expression and promoted sAPPalpha secretion. In addition, GL extracts activated ERK1/2 and PKC phosphorylation. The complex signaling cascades of PI3K and ERK may be responsible for GL-mediated sAPPalpha secretion.
Pinweha
Sirinthorn
S
Department of Pharmacology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. psirinthorn@hotmail.com
Wanikiat
Payong
P
Sanvarinda
Yupin
Y
Supavilai
Porntip
P
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D045744:Cell Line, Tumor; D045424:Complex Mixtures / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D020940:Reishi / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*
D016564:Amyloid beta-Protein Precursor; D045424:Complex Mixtures; D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D053829:Amyloid Precursor Protein Secretases